Mepolizumab for Severe Asthma

(REIMAGINE Trial)

Recruiting at 58 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: GlaxoSmithKline

Must be taking: Nucala

Must not be taking: Omalizumab, Reslizumab, Dupilumab, others

Disqualifiers: Maintenance OCS, Interventional study, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

336 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, real-world, single arm, global, multi-centre study to evaluate the effect of timely treatment with mepolizumab (NUCALA) to achieve clinical remission in adult participants with severe asthma with an eosinophilic phenotype (SA-EP).

Will I have to stop taking my current medications?

The trial requires that participants not be on certain medications like maintenance oral corticosteroids or specific biologics such as omalizumab, reslizumab, dupilumab, tezepelumab, or benralizumab within 6 months before joining. If you're on these, you may need to stop them before participating.

What data supports the effectiveness of the drug Mepolizumab for severe asthma?

Research shows that Mepolizumab significantly reduces asthma attacks in patients with severe eosinophilic asthma (a type of asthma with high levels of a specific white blood cell). It also improves symptoms and lung function over time. ^{1 2 3 4 5}

Is mepolizumab safe for humans?

Mepolizumab has been evaluated for safety in patients with severe eosinophilic asthma, and studies have shown it to be generally safe for use in humans. ^{6 7 8 9 10}

How is the drug Mepolizumab different from other asthma treatments?

Mepolizumab is unique because it is an anti-IL-5 antibody specifically designed to treat severe eosinophilic asthma by targeting and reducing eosinophils, a type of white blood cell that contributes to asthma symptoms. This makes it different from other treatments like omalizumab, which targets different pathways in asthma management. ^{2 6 11 12 13}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for adults with severe asthma who have been prescribed NUCALA (mepolizumab) and haven't used it in the last 6 months. Participants should be able to breathe out at least 60% of what's expected in one second and have had no more than 4 severe asthma attacks per year.

Inclusion Criteria

I haven't used NUCALA in the last 6 months.

Participants with ≥60% predicted forced expiratory volume in 1 second (FEV1) and ≤4 exacerbations per year, as confirmed by the physician

Written informed consent

Exclusion Criteria

Investigator concerns about participant's willingness to adhere to biologic treatment for any reason (e.g., cost, behavior, difficulty with access to healthcare)

Participants participating in an interventional study with a treatment intervention

I am currently taking maintenance oral or intramuscular corticosteroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mepolizumab as part of routine care for severe asthma

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Mepolizumab

Trial Overview The REIMAGINE study is testing how well mepolizumab works in the real world for adults with severe eosinophilic asthma. It's a global study where everyone gets mepolizumab, and doctors check if patients reach 'clinical remission,' meaning their symptoms are under control or gone.

Participant Groups

Group I: Group 1 Experimental Treatment 2 Interventions

Participants with a clinical diagnosis of Severe asthma prescribed Mepolizumab as part of routine care.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

In a study of 204 severe asthmatics treated with either mepolizumab or benralizumab, both medications significantly improved asthma control and reduced exacerbations after 6 and 12 months.

However, benralizumab was found to be more effective than mepolizumab, showing greater improvements in lung function (FEV1) and a more substantial reduction in blood eosinophil counts, indicating its potential as a superior treatment option for severe eosinophilic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benralizumab and mepolizumab treatment outcomes in two severe asthma clinics. Langton, D., Politis, J., Collyer, T., et al.[2023]

In a 32-week trial involving 145 patients with severe eosinophilic asthma who were not optimally controlled on omalizumab, switching to mepolizumab resulted in significant improvements in asthma control, as indicated by a reduction in the Asthma Control Questionnaire (ACQ-5) score by an average of 1.45 points.

Patients also experienced a 64% reduction in the annualized rate of asthma exacerbations, from 3.26 to 1.18 events per year, demonstrating the efficacy of mepolizumab in managing severe asthma symptoms without any reported safety issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma. Chapman, KR., Albers, FC., Chipps, B., et al.[2021]

In a study of 1,192 patients with severe eosinophilic asthma, mepolizumab was shown to significantly reduce exacerbations, but continuation of treatment should not solely rely on short-term assessments like physician-rated responses or lung function tests at week 16.

The best indicators for continuing mepolizumab treatment are the initial criteria of having two or more exacerbations in the previous year and elevated blood eosinophil counts, rather than short-term changes in eosinophil levels or asthma control scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Potential Continuation Rules for Mepolizumab Treatment of Severe Eosinophilic Asthma. Gunsoy, NB., Cockle, SM., Yancey, SW., et al.[2019]

In a study of 21 patients with severe eosinophilic asthma, mepolizumab treatment significantly reduced eosinophil levels and improved pulmonary function, as indicated by increased FEV1 values after 12 months.

Mepolizumab also decreased the frequency of asthma attacks and hospital admissions, with over half of the patients classified as responders, demonstrating its efficacy in managing severe eosinophilic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of mepolizumab in patients with severe eosinophilic asthma: In a real life study]. Bulut, İ., Yegin Katran, Z., Yavuz, D., et al.[2023]

In a phase IV study of patients with severe refractory T2-high asthma treated with mepolizumab, significant improvements in asthma control and lung function were observed after 12 months, with a 71.22% reduction in asthma exacerbations.

Mepolizumab was found to be safe, with only 3.27% of patients discontinuing treatment due to musculoskeletal disorders, indicating its potential as an effective add-on therapy for this asthma phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Performance of Mepolizumab in T2-High Severe Refractory Asthma with the Overlapping Eosinophilic-Allergic Phenotype. González-Pérez, R., Poza-Guedes, P., Mederos-Luis, E., et al.[2023]

In a study of patients with severe asthma at the Cleveland Clinic, 17% discontinued mepolizumab therapy within 6 months, with an average discontinuation time of 5.8 months for those who stopped.

Factors such as a low Asthma Control Test (ACT) score and being male significantly increased the likelihood of discontinuing mepolizumab, suggesting that these characteristics may help identify patients who might not benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of ACT Score in Mepolizumab Discontinuation. Solanki, N., Beck, B., Labadia, M., et al.[2023]

In a study of 31 patients with severe eosinophilic asthma treated with mepolizumab, 83.87% showed a positive response to the treatment, indicating its effectiveness in real-world settings.

The treatment led to significant improvements, including over 80% reduction in blood eosinophils for 87.1% of patients and a 30% decrease in exacerbation rates for 96.77%, demonstrating that mepolizumab is effective even in patients with comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life effectiveness of mepolizumab in patients with severe refractory eosinophilic asthma and multiple comorbidities. Crimi, C., Campisi, R., Cacopardo, G., et al.[2022]

Mepolizumab significantly reduced the rate of clinically significant asthma exacerbations in Korean patients with severe eosinophilic asthma, demonstrating its efficacy in this population.

The safety profile of mepolizumab in Korean patients was consistent with that observed in the overall population, indicating it is a safe treatment option for severe eosinophilic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies. Kim, MK., Park, HS., Park, CS., et al.[2021]

In a study of 20 adults with severe eosinophilic asthma, treatment with mepolizumab led to significant improvements in asthma control and small airway function within just 4 weeks, with benefits sustained at 26 weeks.

The improvement in small airway function, measured by Sacin, was correlated with better symptom control, suggesting that addressing small airway issues may be key to the therapeutic effects of mepolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab improves small airway function in severe eosinophilic asthma. Farah, CS., Badal, T., Reed, N., et al.[2020]

In a study of 23 patients with severe eosinophilic asthma, mepolizumab significantly reduced exacerbation frequency by 87%, with 82.6% of patients experiencing fewer attacks, and 11 patients having no exacerbations during treatment.

The treatment also led to a reduction in the use of oral corticosteroids, with 60% of patients decreasing their dosage and 26.7% completely stopping their use, while mild adverse effects like headache and dizziness were reported in about half of the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of mepolizumab in severe refractory eosinophilic asthma: results in clinical practice. Montero-Pérez, O., Contreras-Rey, MB., Sánchez-Gómez, E.[2022]

In a study of 245 patients with severe asthma, 88% were found to have severe asthma, with 61% of these patients exhibiting an eosinophilic phenotype, making them potential candidates for mepolizumab therapy.

Children with severe asthma were less likely to be eligible for mepolizumab compared to adults, with only 33% of children qualifying based on eosinophil counts, while adults showed distinct phenotypic features such as higher eosinophil levels and nasal polyps that favored treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proportion of Severe Asthma Patients Eligible for Mepolizumab Therapy by Age and Age of Onset of Asthma. Comberiati, P., McCormack, K., Malka-Rais, J., et al.[2020]

Mepolizumab is a humanized anti-interleukin-5 monoclonal antibody that has been available in Switzerland since 2016, specifically designed to treat severe eosinophilic asthma in adults.

There is a significant need for new therapies in severe asthma that are both effective and have a good safety profile, highlighting the importance of mepolizumab and other monoclonal antibodies like dupilumab in asthma treatment development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Innovations in the treatment of severe asthma]. Buss, G., Spertini, F.[2019]

In a study of 55 patients with severe eosinophilic asthma, mepolizumab treatment significantly reduced asthma exacerbations, oral corticosteroid use, and hospitalization rates, while improving lung function and asthma control scores.

Baseline eosinophil count, eosinophil/lymphocyte ratio, and FEV1 values were identified as key predictors of how well patients responded to mepolizumab, indicating that these factors could help tailor treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Clinical Features and Laboratory Data of Patients with Severe Eosinophilic Asthma Classified as Super-Responders, Partial Responders, or Nonresponders to Mepolizumab Treatment: A Real-Life Study. Cakmak, ME., Öztop, N., Yeğit, OO., et al.[2023]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Benralizumab and mepolizumab treatment outcomes in two severe asthma clinics. [2023]

2. Denmark pubmed.ncbi.nlm.nih.gov

The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Potential Continuation Rules for Mepolizumab Treatment of Severe Eosinophilic Asthma. [2019]

4. Turkey pubmed.ncbi.nlm.nih.gov

[Effectiveness of mepolizumab in patients with severe eosinophilic asthma: In a real life study]. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Life Performance of Mepolizumab in T2-High Severe Refractory Asthma with the Overlapping Eosinophilic-Allergic Phenotype. [2023]

6. England pubmed.ncbi.nlm.nih.gov

The Role of ACT Score in Mepolizumab Discontinuation. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Real-life effectiveness of mepolizumab in patients with severe refractory eosinophilic asthma and multiple comorbidities. [2022]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Mepolizumab improves small airway function in severe eosinophilic asthma. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of mepolizumab in severe refractory eosinophilic asthma: results in clinical practice. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Proportion of Severe Asthma Patients Eligible for Mepolizumab Therapy by Age and Age of Onset of Asthma. [2020]

12. Switzerland pubmed.ncbi.nlm.nih.gov

[Innovations in the treatment of severe asthma]. [2019]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of the Clinical Features and Laboratory Data of Patients with Severe Eosinophilic Asthma Classified as Super-Responders, Partial Responders, or Nonresponders to Mepolizumab Treatment: A Real-Life Study. [2023]